Effects of p38 MAPK inhibition on early stages of diabetic retinopathy and sensory nerve function.

@article{Du2010EffectsOP,
  title={Effects of p38 MAPK inhibition on early stages of diabetic retinopathy and sensory nerve function.},
  author={Yunpeng Du and Jie-long Tang and Guangyuan Li and Liliana N. Berti-Mattera and CHIEH-ALLEN Lee and Darian M Bartkowski and David C. Gale and Joseph B. Monahan and Michael R. Niesman and Gordon R Alton and Timothy S. Kern},
  journal={Investigative ophthalmology \& visual science},
  year={2010},
  volume={51 4},
  pages={
          2158-64
        }
}
Purpose. p38 mitogen-activated protein kinase (MAPK) is known to play a regulatory role in inflammatory processes in disease. Inflammation has been linked also to the development of diabetic retinopathy in rodents. This study was conducted to evaluate the effect of a p38 MAPK inhibitor on the development of early stages of diabetic retinopathy in rats. Methods. Streptozotocin-diabetic rats were assigned to two groups-treated with the p38 MAPK inhibitor PHA666859 (Pfizer, New York, NY) and… 
View on PubMed
europepmc.org
109 Citations
Highly Influential Citations
6
Background Citations
41
Methods Citations
8
Results Citations
1

Figures and Tables from this paper

109 Citations

The role of Raf-1 kinase in diabetic retinopathy
TLDR
Further elucidating the role of Raf kinase in diabetic retinopathy, and advances in the generation of antisense therapy for chronic diseases, should help test Raf antisense oligonucleotides for the treatment of this blinding complication that diabetic patients fear the most.
Gallic acid ameliorates renal functions by inhibiting the activation of p38 MAPK in experimentally induced type 2 diabetic rats and cultured rat proximal tubular epithelial cells.
12/15-Lipoxygenase inhibition counteracts MAPK phosphorylation in mouse and cell culture models of diabetic peripheral neuropathy.
TLDR
12/ 15-lipoxygenase inhibition counteracts diabetes related MAPK phosphorylation in mouse and cell culture models of diabetic neuropathy and implies that 12/15-lip Oxygenase inhibitors may be an effective treatment for diabetic peripheral neuropathy.
Deletion of Aldose Reductase from Mice Inhibits Diabetes-Induced Retinal Capillary Degeneration and Superoxide Generation
TLDR
Deletion of the enzyme inhibits the diabetes-induced increase in expression of iNOS and of superoxide production, but does not correct a variety of other pro-inflammatory abnormalities associated with the development of diabetic retinopathy.
Histamine causes an imbalance between pro-angiogenic and anti-angiogenic factors in the retinal pigment epithelium of diabetic retina via H4 receptor/p38 MAPK axis
TLDR
HRH4 was a critical regulator of VEGF, IL-6 and PEDF in the RPE under hyperglycemic conditions and the p38 mitogen-activated protein kinase pathway mediated this regulatory mechanism.
Metanx and early stages of diabetic retinopathy.
TLDR
Investigation of the effect of Metanx against development of early stages of diabetic retinopathy in a mouse model found it inhibited a diabetes-induced defect in retinal spatial frequency threshold and inhibited measures of oxidative stress and inflammation.
Diabetic retinopathy and signaling mechanism for activation of matrix metalloproteinase‐9
TLDR
Results suggest that Ras/Raf‐1/MEK/ERK cascade has an important role in the activation of retinal MMP9 resulting in the apoptosis of its capillary cells.
Photobiomodulation Inhibits Long-term Structural and Functional Lesions of Diabetic Retinopathy
TLDR
Photobiomodulation significantly inhibits the functional and histopathologic features of early DR, and these effects likely are mediated via multiple mechanisms.
Curcumolide reduces diabetic retinal vascular leukostasis and leakage partly via inhibition of the p38MAPK/NF-κ B signaling.
Pro-inflammatory cytokines downregulate Hsp 27 and cause apoptosis of human retinal capillary endothelial cells
TLDR
It is suggested that pro-inflammatory cytokines induce the formation of ROS and NO, which, through theformation of peroxynitrite, reduce the Hsp27 content and bring about apoptosis of retinal capillary endothelial cells.
...
...

References

SHOWING 1-10 OF 59 REFERENCES
Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy
TLDR
Increased p38 MAPK signalling is a feature of human and experimental diabetic nephropathy and time course studies in mouse models suggest that phosphorylation of p38 plays a pathological role, particularly in the development of interstitial fibrosis.
Contributions of Inflammatory Processes to the Development of the Early Stages of Diabetic Retinopathy
  • T. Kern
  • Medicine, Biology
    Experimental diabetes research
  • 2007
TLDR
This new hypothesis offers new insight into the pathogenesis of diabetic retinopathy, and offers novel targets to inhibit the ocular disease.
Salicylate-Based Anti-Inflammatory Drugs Inhibit the Early Lesion of Diabetic Retinopathy
TLDR
Salicylates, in doses administrated in the authors' experiments, inhibited NF-κB and perhaps other transcription factors in the retina, were well tolerated, and offered new tools to investigate and inhibit the development of diabetic retinopathy.
Interaction between NO and COX pathways in retinal cells exposed to elevated glucose and retina of diabetic rats.
  • Yunpeng DuV. SarthyT. Kern
  • Biology, Medicine
    American journal of physiology. Regulatory, integrative and comparative physiology
  • 2004
TLDR
In vitro results suggest that the hyperglycemia-induced increase in NO in retinal Müller cells and endothelial cells increases production of cytotoxic prostaglandins via COX-2 and that inhibition of retinopathy by aminoguanidine or aspirin is due at least in part to inhibition of this NO/COX- 2 axis.
Characterization of activation of MAP kinase superfamily in vasculature from diabetic rats.
TLDR
The results suggest that, under diabetic conditions, the MAP kinase superfamily was activated by different pathways in the vasculature, but the phosphorylation of JNK-1 might depend on the concentration of proinflammatory cytokines such as IL-1beta, and/or additional unknown factors, except glucose.
Duration of streptozotocin-induced diabetes differentially affects p38-mitogen-activated protein kinase (MAPK) phosphorylation in renal and vascular dysfunction
TLDR
Evidence is provided that diabetes produces vascular and renal dysfunction with a profound effect on signaling mechanisms at later stage of diabetes and an up-regulation of inducible nitric oxide synthase, prepro endothelin-1 and phosphorylated p38-MAPK in thoracic aorta and kidney cortex but not in kidney medulla in 28-days diabetes group.
Response of capillary cell death to aminoguanidine predicts the development of retinopathy: comparison of diabetes and galactosemia.
TLDR
The frequency of early apoptosis in retinal microvascular cells predicted the development of the histologic lesions of retinopathy in diabetes as well as in galactosemia, and the beneficial effect of AMG on retinal lesions in diabetes is exerted on pathways that are either not operative or are less important in galACTosemia and that may not relate to the accumulation of AGEs.
Pharmacological inhibition of diabetic retinopathy: aminoguanidine and aspirin.
TLDR
Administration of aminoguanidine essentially prevented the retinopathy, significantly inhibiting the development of retinal microaneurysms, acellular capillaries, and pericyte ghosts compared with diabetic controls.
Effects of p38 MAPK Inhibitor on Angiotensin II-Dependent Hypertension, Organ Damage, and Superoxide Anion Production
TLDR
The results suggest that Ang II induced hypertension, organ damage, and ROS production are possibly mediated by p38 MAPK and inhibition of p38MAPK may offer a therapeutic approach for cardiovascular disease.
p38MAPK and ERK promote nitric oxide production in cultured human retinal pigmented epithelial cells induced by high concentration glucose.
...
...